Diastereoselective Synthesis of Lincosamine Precursors

Abstract

The stereoselective syntheses of the four aminodiol precursors of the diastereomers of lincosamine are reported. The procedure is based on the initial two‐carbon elongationof 1,2;3,4‐di‐O‐isopropylidene‐α‐D‐galactohexodialdo‐1,5‐pyranose, followed by the stereocontrolled introduction of the amino group by nucleophilic amination. Two complementary approaches have been investigated and compared: The first one is the direct transformation of α‐chloroglycidic ester into β‐amino‐α‐keto ester. The second strategy is a three‐step synthesis that is based on the treatment of the β‐iodo‐α‐keto ester with dibenzylamine. Subsequent reduction of the β‐amino‐α‐keto ester provides the pure D‐erythro, L‐threo, L‐erythro, and D‐threo aminodiols after chromatographic purification. Further classical transformations afford the N‐acetyl derivatives, which are key precursors of the lincosamine diastereomers.

A Representative Synthetic Route for C5 Angucycline Glycosides: Studies Directed toward the Total Synthesis of Mayamycin

“…The driving force could be the product stability. The absence of 3H of one CH 3 in the 1 H NMR spectrum and absence of CO and one CH 3 in the 13 C NMR spectrum suggested the structure of compound 43, and finally it was confirmed by HRMS spectral data.…”

“…For the synthesis of a sugar-containing naphthalenone (cf. 14 ), we chose easily accessible galactose aldehyde 16 (Scheme ). It was reacted with the Grignard reagent, prepared by treating bromoarene 17 with magnesium metal in refluxing tetrahydrofuran (THF), to furnish alcohol 18 as a 7:10 mixture of diastereoisomers.…”

Efficient Synthesis of Direct Precursors of the Carbohydrate Moiety of New Antibacterials 6-Epi-VIC-105555 and 6-Epi-VIC-II

“…From this mixture epimer 14-Dglycero can be isolated in pure form, although the separation is difficult. [15] In this study, therefore, we use 14-L -glycero as starting material, as this epimer can be much more easily obtained. Additionally, in the preparation of precursor of the carbohydrate moiety of 6-epi-VIC-105555, mixture 14-L -glycero/14-D -glycero is also tested.…”

“…The β-dibenzylamino-α-ketoester 14-L -glycero and 14-D -glycero were synthesized using our procedure described earlier. [15] General Procedure for the Olefination Reaction…”

Exploring the Chemistry of Non‐sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d‐Allopyranose

“…Thus, azide 33 was reduced with H 2 gas and a catalytic amount of palladium to generate amine 35 . The latter was directly subjected to a reductive amination with 1,2:3,4‐di‐ O ‐isopropylidene‐α‐ d ‐galacto‐hexodialdo‐1,5‐pyranose 36 and NaBH 3 CN to afford the first 3‐amino‐bridged fluorinated disaccharide 15 in 47 % over two steps. Unnatural disaccharides are needed as potential drug candidates and for investigation of biochemical processes.…”